The cytolytic action of complement is mediated by components C5, C6, C7, C8 and C9. Following activation of C5 by the C4, 2, 3 enzyme, these complement components become assembled into a macromolecular structure designated C5-9. When this process takes place on the surface of susceptible cells, membrane damage is produced. Our research program is designed to determine how C5-9 damages cell membranes. We have developed a series of immunological, enzymological, radiochemical and other biochemical approaches to this problem. It is our aim to determine whether the C5-9 assembly is bound on the surface of the cell membrane or whether polypeptide chains from its subunits penetrate into the internal structure of the membrane. Accordingly, a major part of our work involves studies of the possible insertion of polypeptide chains from C5-9 into phospholipid bilayers. We have already obtained tentative evidence indicating such insertion. We plan to extend this work in order to examine the validity of these preliminary results. If confirmed, we plan to study how such insertion takes place and how the inserted polypeptide chains impair the integrity of the cell membrane. Studies may also be performed on activation of the C5-9 sequence by the properdin pathway. BIBLIOGRAPHIC REFERENCES: Michaels, David W., Abramovitz, Aaron S., Hammer, Carl H. and Mayer, Manfred M. Increased Ion Permeability of Planar Lipid Bilayer Membranes After Treatment with the C5b-9 Cytolytic Attack Mechanism of Complement. Proceedings of the National Academy of Sciences, 73:2852, 1976. Shin, Moon L., Gelfand, M.C., Nagle, R.B., Carlo, J.R., Green, I. and Frank, M.M. Localization of Receptors for Activated Complement on Visceral Epithelial Cells of the Human Renal Glomerulus. Journal of Immunology, 118:869, 1977. Hammer, Carl H., Shin, Moon L., Abramovitz, Aaron S. and Mayer, Manfred M. On the Mechanism of the Cell Membrane Damage by Complement. Evidence on Insertion of Polypeptide Chains from C8 and C9 into the Lipid Bilayer of Erythrocytes. Journal of Immunology, in press, July 1977.